RUI: Mechanisms of Transcriptional Repression by Sequence Specific Transcription Factors

该项目使用一种综合的科学方法来进一步了解细胞机制如何在胚胎出生前的生长和发育过程中协调基因表达，并测试从出生到成年的这种协调的计算模型，使科学家能够将基因表达的调节与细胞规格和胚胎形态发生等关键发育事件相关联。通过以课程为基础的本科生研究经验(CURE)和独立指导研究的结合，本科生将使用遗传学、分子生物学、数学建模和人工神经网络来模拟抑制基因表达的蛋白质-DNA相互作用，而硕士学生将从事以学科为基础的教育研究(DBER)，以了解CURE如何提高学生在STEM中的成绩和留存率。这个项目还促进了学生和教职员工与来自传统上在STEM中代表性不足的群体的科学家的接触，通过名为“代表性问题”的研讨会/工作坊系列，旨在增加STEM领域中代表性不足的科学家的留存。该项目的研究目标是了解HES蛋白在胚胎发生过程中介导转录抑制的分子机制，并使用这些信息以秀丽线虫为模型系统，在全基因组范围和跨发育阶段检验HES介导的抑制的预测。本科生将使用CHIP-SEQ、RNA-SEQ、RNA干扰和免疫共沉淀来定义HES介导的抑制的顺式和跨式调节环境。硕士研究生和博士后将使用CHIP-SEQ和CHIP-PCR来确定HES蛋白的启动子或增强子是否会影响RNA聚合酶的占有率或染色质的状态。这些数据将被用来建立模型，并使用深度学习或神经网络半监督模型来测试胚胎发生期间HES介导的抑制的预测。该项目的更广泛的影响目标是为本科生和硕士学生提供基础研究经验，同时加强对代表不足群体的学生的培训和指导经验。一个多方面的方法，包括有指导的研究经验，强化生物学基本原理并引入计算模型的治疗方法，以及有意促进学生和有色人种科学家之间的专业和社会互动的活动，将检查学生学习、自我认同和社会意识的感知和实际结果。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project uses an integrated sciences approach to further understanding of how the cellular machinery coordinates gene expression as an embryo grows and develops prior to birth and to test computational models of that coordination from birth through adulthood, allowing scientists to correlate the regulation of gene expression with critical developmental events like cellular specification and embryonic morphogenesis. Through a combination of course-based undergraduate research experiences (CUREs) and independent mentored research, undergraduate students will use genetics, molecular biology, mathematical modeling, and artificial neural networks to model protein-DNA interactions that inhibit gene expression, while Masters students will engage in discipline-based education research (DBER) to understand how CUREs promote student outcomes and student retention in STEM. This project also promotes the engagement of students and faculty with scientists from groups that are traditionally underrepresented in STEM, through a seminar/workshop series titled “Representation Matters” that aims to increase the retention of underrepresented scientists in STEM fields.The research objective of this project is to understand the molecular mechanisms by which HES proteins mediate transcriptional repression during embryogenesis and to use that information to test predictions of HES mediated repression genome-wide and across developmental stages, using Caenorhabditis elegans as a model system. Undergraduates students will use ChIP-seq, RNA-seq, RNA-interference, and co-immunoprecipitation to define the cis- and trans-regulatory contexts of HES-mediated repression. Masters students and a postdoctoral fellow will use ChIP-seq and ChiP-PCR to determine if promoter or enhancer occupancy by HES proteins influences RNA polymerase occupancy or chromatin status. These data will be used to build models and to test predictions of HES-mediated repression during embryogenesis using deep learning or neural network semi-supervised models. The broader impacts objective of this project is to provide foundational research experiences for undergraduate and Masters students while enhancing training and mentoring experiences of students from underrepresented groups. A multi-faceted approach that includes mentored research experiences, CUREs that reinforce fundamental principles in biology and that introduce computational modeling, and activities that intentionally promote professional and social interactions between students and scientists of color, will examine perceived and actual outcomes of student learning, self-identification and social awareness.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.